1-Hydroxybenzotriazole → 1-{[1-(Cyclohexylmethyl)-7-methoxy-1H-indol-3-yl]carbonyl}-3-(fluoromethyl) piperazine, hydrochloride salt

HRID 968650노트

반응식

HRID 968650 반응식
[CH:1]1([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[O:17][CH3:18])[C:10]([C:19](O)=[O:20])=[CH:9]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[F:22][CH2:23][CH:24]1[CH2:29][NH:28][CH2:27][CH2:26][NH:25]1.[ClH:30].CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>ClCCl>[ClH:30].[CH:1]1([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[O:17][CH3:18])[C:10]([C:19]([N:28]3[CH2:27][CH2:26][NH:25][CH:24]([CH2:23][F:22])[CH2:29]3)=[O:20])=[CH:9]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

참가 물질

6

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 14479501HCID 14479501, 화합물HCID 686950531-(Cyclohexylmethyl)-7-methoxyindole-3-carboxylic acid

생성물 1

HCID 1317267041-{[1-(Cyclohexylmethyl)-7-methoxy-1H-indol-3-yl]carbonyl}-3-(fluoromethyl) piperazine, hydrochloride salt

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of 1-(cyclohexyl)methyl-7-methoxy-indole-3-carboxylic acid (0.59 g, 2.04 mmol, prepared following the method in Example 1) and 2-(fluoromethyl) piperazine (0.37 g, 3.15 mmol) in dichloromethane (15 ml) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.47 g, 2.45 mmol) and 1-hydroxy benzotriazole (0.07 g, 0.51 mmol). The mixture was stirred at room temperature for 18 h and evaporated. The residue was purified by flash chromatography eluting with 0-10% (v/v) methanol in dichloromethane to afford the title compound (free base) as a colourless oil (0.47 g). The free base (0.05 g) was dissolved in diethyl ether (3 ml) and treated dropwise with 2 M hydrochloric acid in diethyl ether (1 ml). The resulting precipitate was collected by filtration, washed with diethyl ether (10 ml) and dried under reduced pressure to afford the title compound (1:1 hydrochloric acid salt) as a colourless solid (0.05 g, 0.12 mmol). 1H NMR (400 MHz, CD3OD) δH 0.98-1.27 (5H, m), 1.57 (2H, br d, J 12.9), 1.63-1.90 (4H, m), 3.21-3.53 (4H, m), 3.68-3.79 (1H, m) 3.95 (3H, s), 4.26 (2H, d, J 7.1), 4.43-4.82 (4H, m), 6.77 (1H, d, J 7.7), 7.11 (1H, t, J 7.5), 7.27 (1H, d, J 8.0), 7.57 (1H, s); EIMS: m/z 270.2 [Fragment+H]+.

후처리

  1. customevaporated
  2. customThe residue was purified by flash chromatography
  3. washeluting with 0-10% (v/v) methanol in dichloromethane

출처 및 근거

ORD 기록
ord-950a29b18fe14ea6aed594c5a778537f
출처 데이터셋
uspto-grants-2007_12
특허 번호
US07304064B2

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